Many cardiovascular and pulmonary disease involve disorders of cell proliferation and differentiation. A program of Excellence in Molecular Biology at U.C.S.F. would focus on these problems by utilizing two of the greatest strengths of our institution - an outstanding group of molecular biologists who have made notable contributions to molecular biology and a Cardiovascular Research Institute that has been dedicated to the study of cardiovascular and pulmonary biology for the last three decades. By bringing these groups together, the Program of the last three decades. By bringing these grouwps together, the Program of Excellence would be the focus for new directions in cardiovascular biology at U.C.S.F. The scientific goals of this proposal are to use the most sophisticated molecular and developmental biology approaches to identify the key molecules that regulate the growth and differentiation of cardiac, vascular and pulmonary tissues, to study the structure and function of these molecules in normal development and in disease: and to discover the precursor cells and cellular interactions that are responsible for formation of the heart and blood vessels. Topic of investigation will include the role of growth factors and their receptors in angiogenesis and cardiogenesis, the structural basis for the function of molecules involved in cardiovascular and pulmonary development, the regulation of gene expression in the developing lung, the identification of cell cycle control genes and their role in proliferative diseases and the function of embryonic isoforms of myofibrillar cardiac proteins. In the Skills Development Program young investigators will be instructed in techniques such as the creation of genetically altered mice by "gene targeting" using homologous recombination in embryonic stem cells, expression and subtractive cDNA cloning, x-ray crystallography, in situ hybridization, site-directed and saturation mutagenesis, and the use of large scale systems for expression of proteins. They will also learn novel approaches to developmental biology. The Program of Excellence will establish a unique advanced investigator program that will support young investigators after their postdoctoral training. Thus the Progrram will provide the opportunity for development of new research directions and will produce a new generation of molecular biologists workintg in cardiovascular and pulmonary biology.